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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1007/s11075-014-9869-1

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1573-904X

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Curcumin Inhibits the Activity of ABCG2/BCRP1 a M

Authors: Suneet Shukla Hani Zaher Anika Hartz Björn Bauer Joseph A Ware Suresh V Ambudkar
Publish Date: 2008/10/09
Volume: 26, Issue: 2, Pages: 480-487
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Abstract

Photoaffinity labeling with 125Iiodoarylazidoprazosin was used to characterize the interaction of sulfasalazine a substrate of the mouse ABCG2 with human ABCG2 In addition the inhibitory effect of curcumin on ABCG2 was evaluated in brain capillaries from rats Furthermore the effect of curcumin on absorption of orally administered sulfasalazine in wildtype and abcg2 −/− mice was also determinedSulfasalazine interacted at the drugsubstrate sites of human ABCG2 Curcumin inhibited ABCG2 activity at nanomolar concentrations at the rat bloodbrain barrier in the ex vivo assay Based on studies in wild type and abcg2 −/− mice we observed that oral curcumin increased C max and relative bioavailability of sulfasalazine by selectively inhibiting ABCG2 functionThis study validates our previous in vitro results with human ABCG2 Chearwae et al Mol Cancer Ther 51995–2006 2006 and provides the first in vivo evidence for the inhibition by curcumin of ABCG2mediated efflux of sulfasalazine in mice Based on these studies we propose that nontoxic concentrations of curcumin may be used to enhance drug exposure when the ratelimiting step of drug absorption and/or tissue distribution is impacted by ABCG2This work was supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute Center for Cancer Research We thank Dr Krishnamachary Nandigama for providing ABCG2expressing Hifive insect cell crude membranes and George Leiman for editorial assistance The authors wish to acknowledge the contribution of Joe Palandra of Pfizer Global Research and Development for his assistance in determination of SASP bioanalysis and for the input of Lisa Bernstein Nonclinical Biostatistics Genentech Inc

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